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Introduction: After a previous caesarean section, morbidity in the subsequent delivery in general is considered to depend on the probability of a vaginal birth after caesarean. However counselling could be improved by adding individualized probability of serious morbidity following either trial of labour or elective repeat caesarean section. The objective of this study was to develop prediction models for morbidity for both a repeat caesarean section and a trial of labor for a Dutch population., Material and Methods: In this cohort study, data were joined from three previous studies (SIMPLE 1, SIMPLE 2 and SIMPLE 2-implementation study). A cohort of 2592 women with one previous caesarean section and a singleton pregnancy who delivered ≥37 weeks, without a contraindication for vaginal delivery was formed. Maternal morbidity was defined as postpartum hemorrhage, blood transfusion, uterine rupture, ICU admittance or death. Neonatal morbidity was defined as asphyxia, NICU-admittance or death. Potential predictors for morbidity were chosen based on literature and expert opinion. Logistic regression was used to develop the models. Internal validation was intended using bootstrapping techniques. Main outcome measures were predictors for morbidity and for validation of the model we used the area under the receiver operating characteristic curve for discriminative capacity and calibration for accuracy., Results: In 324 out of the 2592 cases (12.7 %) maternal or fetal complications occurred. In general total morbidity was higher in women choosing TOL as compared to ERCS (p < 0.001). The performance of the several developed models was insufficient, the area under the receiver operating characteristic curve did not rise above 0.6. Due to poor model performance, before correction for overfitting, interval validation was not conducted., Conclusion: In this large cohort, developing a Dutch population based prediction model that aimed to improve counselling on the mode of delivery, by predicting individual chances of morbidity for different delivery modes was not possible, due to lack of performance. Further study could be directed to cut off on VBAC success rates to a more general advice regarding the safest mode of delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Various industries produce a myriad of synthetic molecules used to satisfy our needs, but all these molecules are likely to reach aquatic environments. The number of organic contaminants found in rivers and lakes continues to rise, and part of this contamination gets transferred into sediments. Analytical methods to detect problematic substances in the environment often use mass spectrometry coupled with chromatography. Here we reviewed a set of 163 articles and compiled the relevant information into a comprehensive database for analysing organic contaminants in continental sediments including suspended particulate matter and surface and bottom sediments in lakes, rivers and estuaries. We found 1204 compounds detected at least once in sediments, and classified them into 11 categories, i.e. hydrocarbons, flame retardants, polychlorinated biphenyls (PCB), plasticizers, per- and poly-fluoroalkyl substances (PFAS), organochlorines (OCP) and other pesticides, pharmaceuticals, hormones, personal care products (PCP), and other contaminants. Concentrations of these compounds varied from a few ng to several mg/kg of dry sediment. Even hydrophilic compounds were detected in high concentrations. Well-known hydrophobic and persistent contaminants tend to be analysed with mass spectrometry coupled to gas chromatography (GC-MS) whereas contaminants of emerging concern (CEC) are usually analysed with liquid chromatography- mass spectrometry (LC-MS). Suspect screening and non-target analysis (NTA), which use high-resolution mass spectrometry, are still scarcely used on sediment but hold promise for gaining deeper knowledge of organic contamination in aquatic environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background Internal medicine residents frequently experience distressing clinical events; critical event debriefing is one tool to help mitigate their effects. Objective To evaluate the effectiveness of a 1-hour workshop teaching residents a novel, efficient approach to leading a team debrief after emotionally charged clinical events. Methods An internal needs assessment identified time and confidence as debriefing barriers. In response, we created the STREAM (Structured, Timely, Reflection, tEAM-based) framework, a 15-minute structured approach to leading a debrief. Senior residents participated in a 1-hour workshop on the first day of an inpatient medicine rotation to learn the STREAM framework. To evaluate learning outcomes, participants completed the same survey immediately before and after the session, and at the end of their 4-week rotation. Senior residents at another site who did not complete the workshop also evaluated their comfort leading debriefs. Results Fifty out of 65 senior residents (77%) participated in the workshop. After the workshop, participants felt more prepared to lead debriefs, learned a structured format for debriefing, and felt they had enough time to lead debriefs. Thirty-four of 50 (68%) workshop participants and 20 of 41 (49%) comparison residents completed the end-of-rotation survey. Senior residents who participated in the workshop were more likely than nonparticipants to report feeling prepared to lead debriefs. Conclusions A brief workshop is an effective method for teaching a framework for leading a team debrief.

An increasing body of evidence suggests that complaints of fatigue among healthcare staff is widespread and rising, owing to a combination of high work intensity, understaffed workplace and nightshift working. This has been linked to poorer outcomes for patients and to increased risks of injuries for practitioners. Fatiguedecreases performance andphysicalandmentalwellbeing. Moreover, it can lead to sickness absence. What lies behind this culture, behaviour and what are possible solutions to this? A committee called I'm Safe, assigned by the Dutch Association of Anaesthesiology, will address these issues, raise awareness and inform physicians about the impact of shift working. Its aim is to provide tools on where changes can be made in order to create a healthier work environment.

The growing application of high resolution mass spectrometry (HRMS) over the last decades has dramatically improved our knowledge about the occurrence of environmental contaminants. However, most of the compounds detected remain unknown and the large volume of data generated requires specific processing approaches. Therefore, this study presents the concepts of mass defect (MD), Kendrick mass (KM) and Kendrick mass defect (KMD) to the expert and non-expert reader along with relevant examples of applications in environmental HRMS data processing. A preliminary bibliometric overview indicates that the potential benefits of KMD analysis are rather overlooked in environmental science. In practice, a simple calculation allows transforming a mass from the IUPAC system (normalized so that the mass of 12 C is exactly 12) to its corresponding KM normalized on a specific moiety such as CH 2 (the mass of CH 2 is exactly 14). Then, plotting the KMD according to the nominal KM allows revealing groups of compounds that differ only by their number of CH 2 moieties. For instance, data processing using KM and KMD was proven particularly useful to characterize natural organic matter in a sample, to reveal the occurrence of polymers as well as poly/perfluorinated alkylated substances (PFASs), and to search for transformation products (TPs) of a given chemical., Competing Interests: Declaration of competing interest The author declares that there are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mealtime is a parent-toddler interaction that occurs multiple times a day. This study examined whether observed maternal sensitivity differed between a mealtime and free-play setting, aiming to explain differences between the two situations by studying moderating effects of children's eating behavior. The sample consisted of 103 first-time mothers and their 18-month-old children. Maternal sensitivity was assessed by coding videotaped interactions of free-play sessions and mealtimes, using the Ainsworth Sensitivity Scale (range 1-9). Additionally, child eating behavior during the meal was coded and also assessed through the Child Eating Behavior Questionnaire-Toddlers. First, a small but significant amount of stability was found between sensitivity during mealtime and sensitivity during play (r = 0.24). Second, mothers were more sensitive during free play (mean = 7.11) than during mealtime (mean = 6.52). Third, observed child eating behavior was related to maternal sensitivity during mealtime, with more food enjoyment being associated with higher levels of sensitivity, and more challenging child behavior with lower levels of sensitivity. Finally, when children showed a high degree of challenging behavior during the meal, there was more discrepancy between sensitivity during mealtime and free play. Our results highlight the importance of taking context into account when observing parental sensitivity., (© 2022 The Authors. Infancy published by Wiley Periodicals LLC on behalf of International Congress of Infant Studies.)

Non-target analysis (NTA) employing high-resolution mass spectrometry is a commonly applied approach for the detection of novel chemicals of emerging concern in complex environmental samples. NTA typically results in large and information-rich datasets that require computer aided (ideally automated) strategies for their processing and interpretation. Such strategies do however raise the challenge of reproducibility between and within different processing workflows. An effective strategy to mitigate such problems is the implementation of inter-laboratory studies (ILS) with the aim to evaluate different workflows and agree on harmonized/standardized quality control procedures. Here we present the data generated during such an ILS. This study was organized through the Norman Network and included 21 participants from 11 countries. A set of samples based on the passive sampling of drinking water pre and post treatment was shipped to all the participating laboratories for analysis, using one pre-defined method and one locally (i.e. in-house) developed method. The data generated represents a valuable resource (i.e. benchmark) for future developments of algorithms and workflows for NTA experiments., (© 2021. The Author(s).)

Wastewater is a significant environmental and public health concern which management is a constant challenge since antiquity. Wastewater research has increased exponentially over the last decades. This paper provides a global overview of the exponentially increasing wastewater research in order to identify current challenges and paradigm shifts. Besides households, hospitals and typical industries, other sources of wastewater appear due to emerging activities like hydraulic fracturing. While the composition of wastewater needs constant reassessment to identify contaminants of interest, the comprehensive chemical and toxicological analysis remains one of the main challenges in wastewater research. Moreover, recent changes in the public perception of wastewater has led to several paradigm shifts: i) water reuse considering wastewater as a water resource rather than a hazardous waste, ii) wastewater-based epidemiology considering wastewater as a source of information regarding the overall health of a population through the analysis of specific biomarkers, iii) circular economy through the implementation of treatment processes aiming at harvesting valuable components such as precious metals or producing valuable goods such as biofuel. However, wastewater research should also address social challenges such as the public acceptance of water reuse or the access to basic sanitation that is not available for nearly a third of the world population., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients., Methods and Analysis: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence., Ethics and Dissemination: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ethoxyquin (EQ) is an additive present in fish feed and its fate in fish should be carefully characterized due to food safety concerns regarding this compound. Therefore, the objective of this work was to identify the transformation products (TPs) of EQ in Atlantic salmon. Salmon in independent tanks were given feed containing ethoxyquin concentrations of 0.5 mg/kg, 119 mg/kg or 1173 mg/kg for 90 days. After the feeding trial, salmon fillets were extracted in acetonitrile and analyzed by liquid chromatography with traveling-wave ion mobility spectrometry coupled to high resolution mass spectrometry (UHPLC-TWIMS-QTOFMS). EQ was transferred from the feed to salmon fillets and 23 TPs were characterized, resulting from dimerization, oxygenation, cleavage, cleavage combined with oxygenation, cleavage combined with conjugation, and other uncategorized alterations. Moreover, EQ and some TPs were also detected in commercial salmon randomly sampled from different Norwegian fish farms. This study confirmed that the dimer 1,8'-EQDM was the main TP of EQ and, together with previous research, brought the overall number of characterized TPs to a total of 47., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The application of nontargeted strategies based on high-resolution mass spectrometry (HRMS) directed toward the discovery of metabolites of known contaminants in fish is an interesting alternative to true nontarget screening. To reduce prolonged and costly laboratory experiments, recent advances in computing power have permitted the development of comprehensive knowledge-based software to predict the metabolic fate of chemicals. In addition, machine-based learning tools allow the prediction of chromatographic retention times (RT) or collision cross section (CCS) values when using ion mobility spectrometry (IMS). These tools can ease data evaluation and strengthen the confidence in the identification of compounds. The current work explores the capabilities of in silico prediction tools, refined by the use of RT and CCS prediction, to prioritize and facilitate nontarget liquid chromatography (LC)-IMS-HRMS data processing. The fate of the insecticide pirimiphos-methyl (PM) in farmed Atlantic salmon exposed to contaminated feed was used as a case study. The theoretical prediction of 60 potentially relevant biological PM metabolites permitted the prioritization of screening in different salmon tissues (liver, kidney, bile, muscle, and fat) of known and unknown PM metabolites. An average of 43 potential positives was found in the sample matrixes based on the accurate mass of protonated molecules (mass error ≤5 ppm). The application of different tolerance filters for RT (Δ ≤ 2 min) and CCS (Δ ≤ 6%) based on predicted values permitted us to reduce this number up to 66% of the features. Finally, five PM metabolites could be identified; two known metabolites (2-DAMP and N-desethyl PM) were confirmed with a standard, whereas three previously unknown metabolites (2-DAMP glucuronide, didesethyl PM, and hydroxy-2-DAMP glucuronide) were tentatively identified in different matrixes, allowing the first proposition of a metabolic pathway in fish.

Interpreting the fate of wastewater contaminants in streams is difficult because their inputs vary in time and several processes synchronously affect reactive transport. We present a method to disentangle the various influences by performing a conservative-tracer test while sampling a stream section at various locations for chemical analysis of micropollutants. By comparing the outflow concentrations of contaminants with the tracer signal convoluted by the inflow time series, we estimated reaction rate coefficients and calculated the contaminant removal along a river section. The method was tested at River Steinlach, Germany, where 38 contaminants were monitored. Comparing day-time and night-time experiments allowed distinguishing photo-dependent degradation from other elimination processes. While photo-dependent degradation showed to be highly efficient for the removal of metroprolol, bisoprolol, and venlafaxine, its impact on contaminant removal was on a similar scale to the photo-independent processes when averaged over 24 h. For a selection of compounds analyzed in the present study, bio- and photodegradation were higher than in previous field studies. In the Steinlach study, we observed extraordinarily effective removal processes that may be due to the higher proportion of treated wastewater, temperature, DOC and nitrate concentrations, but also a higher surface to volume ratio from low flow conditions that favorizes photodegradation through the shallow water column and a larger transient storage than observed in comparable studies., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

β‑Lactam antibiotics are among the most widely used antibiotics in human medicine and their effects on the aquatic environment - concerning bacterial resistance - are controversially discussed. This study focused on the photolysis of the four β‑lactam antibiotics - amoxicillin, ampicillin, penicillin V and piperacillin - under simulated environmental conditions. It was observed that all investigated β‑lactam antibiotics are photolytically degradable by simulated sunlight (1 kW/m 2 ) with half-lives between 3.2 and 7.0 h. Structure elucidation of transformation products performed with liquid chromatography coupled to high resolution mass spectrometry showed that the hydrolysis of the β‑lactam ring is the primary transformation reaction, followed by the elimination of carboxylic and dimethyl thiazolidine carboxylic acid. Growth inhibition tests on Bacillus subtilis showed the loss of bactericide activity of irradiated solutions of amoxicillin, ampicillin and piperacillin, suggesting the transformation of the β‑lactam ring is responsible for the antibiotic effect. In contrast, the solutions of penicillin V did not show any decline of the antibacterial activity after photolytic degradation, probably due to the formation of still active epimers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Incidence of ischemic stroke and transient ischemic attack in young adults is rising. However, etiology remains unknown in 30-40% of these patients when current classification systems designed for the elderly are used. Our aim was to identify risk factors according to a pediatric approach, which might lead to both better identification of risk factors and provide a stepping stone for the understanding of disease mechanism, particularly in patients currently classified as "unknown etiology". Risk factors of 656 young stroke patients (aged 18-50) of the FUTURE study were categorized according to the "International Pediatric Stroke Study" (IPSS), with stratification on gender, age and stroke of "unknown etiology". Categorization of risk factors into ≥1 IPSS category was possible in 94% of young stroke patients. Chronic systemic conditions were more present in patients aged <35 compared to patients ≥35 (32.6% vs. 15.6%, p < 0.05). Among 226 patients classified as "stroke of unknown etiology" using TOAST, we found risk factors in 199 patients (88%) with the IPSS approach. We identified multiple risk factors linked to other mechanisms of stroke in the young than in the elderly . This can be a valuable starting point to develop an etiologic classification system specifically designed for young stroke patients.

Epidemiological evidence suggests that the incidence of ischaemic stroke in young adults (18-50 years) has increased substantially. These patients have a long life expectancy after stroke, and the costs of long-term care pose huge challenges to health-care systems. Although the current recommendations for treatment of young and old (>50 years) patients with stroke are similar, the optimal management of young adult patients with stroke is unknown. They are usually not included in trials, and specific subanalyses limited to young adult patients with stroke are usually not done, owing to lower incidence of stroke and lower prevalence of vascular risk factors in young adults. Progress has been made in identifying patients with a considerable risk of stroke occurrence, such as those with patent foramen ovale. Future prevention studies might result in a decrease in the incidence of stroke and its sequelae in young adults. The development of guidelines specifically devoted to the management of stroke in young adults will be an important step in achieving this aim., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Carbendazim is a fungicide commonly used as active substance in plant protection products and biocidal products, for instance to protect facades of buildings against fungi. However, the subsequent occurrence of this fungicide and potential endocrine disruptor in the aqueous environment is a major concern. In this study, high resolution mass spectrometry shows that carbendazim can be detected with an increasing abundance from the source to the mouth of the River Rhine. Unexpectedly, the abundance of carbendazim correlates poorly with that of other fungicides used as active ingredients in plant protection products (r 2 of 0.32 for cyproconazole and r 2 of 0.57 for propiconazole) but it correlates linearly with that of pharmaceuticals (r 2 of 0.86 for carbamazepine and r 2 of 0.89 for lamotrigine). These results suggest that the occurrence of carbendazim in surface water comes mainly from the discharge of treated domestic wastewater. This hypothesis is further confirmed by the detection of carbendazim in wastewater effluents (n = 22). In fact, bench-scale leaching tests of textiles and papers revealed that these materials commonly found in households could be a source of carbendazim in domestic wastewater. Moreover, additional river samples collected nearby two paper industries indicate that the discharge of their treated process effluents is also a source of carbendazim in the environment. While characterizing paper and textile as overlooked sources of carbendazim, this study also shows the biocide as a possible ubiquitous wastewater contaminant that would require further systematic and worldwide monitoring due to its toxicological properties., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Patients with Parkinson's disease (PD) often compensate for their motor deficits by guiding their movements visually. A wide range of ocular and visual disorders threatens the patients' ability to benefit optimally from visual feedback. These disorders are common in patients with PD, yet they have received little attention in both research and clinical practice, leading to unnecessary - but possibly treatable - disability. Based on a literature search covering 50 years, we review the range of ocular and visual disorders in patients with PD, and classify these according to anatomical structures of the visual pathway. We discuss six common disorders in more detail: dry eyes; diplopia; glaucoma and glaucoma-like visual problems; impaired contrast and colour vision; visuospatial and visuoperceptual impairments; and visual hallucinations. In addition, we review the effects of PD-related pharmacological and surgical treatments on visual function, and we offer practical recommendations for clinical management. Greater awareness and early recognition of ocular and visual problems in PD might enable timely instalment of tailored treatments, leading to improved patient safety, greater independence, and better quality of life., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Denatonium is one of the bitterest substances known to man and therefore applied in numerous consumer products to prevent an accidental or intentional consumption. So far no information was available on the occurrence of this compound in the environment. A sensitive targeted method was developed and applied to water samples taken in the federal state of Baden-Württemberg, Germany. Denatonium was detected in 100% of the investigated 22 wastewater treatment plant (WWTP) effluents with a maximum concentration of 341 ng L -1 . Additionally, water samples were taken from the Ammer river over a period of one week and all wastewater impacted samples showed denatonium at concentrations up to 195 ng L -1 . Retrospective analysis of high-resolution mass spectrometric measurements of WWTP effluents from Italy and Switzerland confirmed and therefore point to an international occurrence of denatonium as anthropogenic contaminant., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Worldwide, ozonation of secondary wastewater effluents is increasingly considered in order to decrease the load of organic contaminants before environmental discharge. However, despite the constantly growing knowledge of ozonation over the past few years, the characterization of transformation products (TPs) is still a major concern, particularly because such TPs might remain biologically active. It has been shown for selected tertiary amine pharmaceuticals that they react with ozone and form the corresponding N-oxides. This study therefore applies liquid chromatography-high resolution mass spectrometry (LC-HRMS) to assess the overall N-oxide formation during the pilot-scale ozonation of a secondary wastewater effluent from a major city in Germany. Sample analysis by LC-HRMS revealed the occurrence of 1,229 compounds, among which 853 were precursors attenuated by ozone and 165 were TPs. Further examination of precursors and TPs using Kendrick mass and Kendrick mass defect analysis revealed 34 pairs of precursors and products corresponding to a mono-oxygenation. Among these, 27 pairs (16% of all TPs) were consistent with N-oxides since the TP had a higher retention time than the precursor, a characteristic of these compounds. Using high resolution tandem mass spectrometry, 10 of these N-oxides could be identified and were shown to be stable during a subsequent filtration step.

The insect repellent diethyltoluamide (DEET) is among the most frequently detected organic chemical contaminants in water across a wide range of geographies from around the world. These observations are raising critical questions and increasing concerns regarding potential environmental relevance, particularly when the emergence of severe neurological conditions attributed to the Zika virus has increased the use of insect repellents. After dermal application, DEET is washed from the skin when bathing and enters the municipal sewer system before discharge into the environment. Mainly measured by gas chromatography or liquid chromatography coupled to mass spectrometry (GC-MS or LC-MS), more than 200 peer-reviewed publications have already reported concentrations of DEET ranging ng/L to mg/L in several water matrices from North America, Europe, Asia, Oceania, and more recently Africa and South America. While conventional wastewater treatment technology has limited capacity of removal, advanced technologies are capable of better attenuation and could lower the environmental discharge of organic contaminants, including DEET. For instance, adsorption on activated carbon, desalinating membrane processes (nanofiltration and reverse osmosis), ozonation, and advanced oxidation processes can achieve 50% to essentially 100% DEET attenuation. Despite the abundant literature on the topic, the ubiquity of DEET in the environment still raises questions due to the apparent lack of obvious spatio-temporal trends in concentrations measured in surface water, which does not fit the expected usage pattern of insect repellents. Moreover, two recent studies showed discrepancies between the concentrations obtained by GC-MS and LC-MS analyses. While the occurrence of DEET in the environment is well established, the concentrations reported should be interpreted cautiously, considering the disparities in methodologies applied and occurrence patterns observed. Therefore, this manuscript provides a critical overview of the origin of DEET in the environment, the relevant analytical methods, the occurrence reported in peer-reviewed literature, and the attenuation efficacy of water treatment processes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Cylindrospermopsin (CYN) is a potent toxic alkaloid produced by a number of cyanobacteria frequently found in lakes and reservoirs used as drinking water sources. We report for the first time detailed pathways for the degradation of CYN by treatment with ozone. This was accomplished by use of ultra-high-performance liquid chromatography (UHPLC)-quadrupole time-of-flight mass spectrometry (QTOF MS), which revealed that CYN is readily degraded by ozone with at least 36 transformation products. Structural similarities among the major products indicated that the carbon-carbon double bond in the uracil ring of CYN was most susceptible to attack by ozone. Furthermore, the nitrogen functionality associated with the tricyclic guanidine moiety is also involved via a degradation pathway that has not been previously observed. To assess the potential toxicity of ozonation products of CYN, the cytotoxicity of CYN and the mixture of its ozonation products was measured in a human hepatoma cell line (HepG2). The IC50 for CYN at 24 and 48 h incubations was approximately 64.1 and 12.5 μM, respectively; however, the ozonation products of CYN did not exhibit measurable cytotoxicity to human cells. The results indicate ozone is an effective and practical method for CYN attenuation in water treatment without formation of overtly toxic transformation products.

Parkinson's disease is a common neurodegenerative disorder, resulting in both motor and non-motor symptoms that significantly reduce quality of life. Treatment consists of both pharmaceutical and non-pharmaceutical treatment approaches. Neurorehabilitation is an important non-pharmaceutical treatment approach, and a prime component of this is formed by the training of behavioural adaptations that can assist patients to cope better with their motor and non-motor symptoms. Optimal delivery of neurorehabilitation requires a tailor-made, personalized approach. In this review we discuss the great potential for growth in the field of neurorehabilitation. Specifically, we will focus on four relatively new developments: visual rehabilitation (because Parkinson patients are very dependent on optimal vision); cueing delivered by wearable devices (allowing for objective, continuous, and quantitative detection of mobility problems, such that cueing can be delivered effectively in an on-demand manner - i.e., with external cues being delivered only at a time when they are needed most); exergaming (to promote compliance with exercise programs); and telemedicine (allowing for delivery of expert rehabilitation advice to the patient's own home). Evidence in these new fields is growing, based on good clinical trials, fuelling hope that state-of-the-art neurorehabilitation can make a real impact on improving the quality of life of patients affected by Parkinson's disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Import of peroxisomal matrix proteins, crucial for peroxisome biogenesis, is mediated by the cytosolic receptors PEX5 and PEX7 that recognize proteins carrying peroxisomal targeting signals 1 or 2 (PTS1 or PTS2), respectively. Mutations in PEX5 or 12 other PEX genes cause peroxisome biogenesis disorders, collectively named the Zellweger spectrum disorders (ZSDs), whereas mutations in PEX7 cause rhizomelic chondrodysplasia punctata type 1 (RCDP1). Three additional RCDP types, RCDP2-3-4, are caused, respectively, by mutations in GNPAT, AGPS and FAR1, encoding enzymes involved in plasmalogen biosynthesis. Here we report a fifth type of RCDP (RCDP5) caused by a novel mutation in PEX5. In four patients with RCDP from two independent families, we identified a homozygous frame shift mutation c.722dupA (p.Val242Glyfs(∗)33) in PEX5 (GenBank: NM&#95;001131023.1). PEX5 encodes two isoforms, PEX5L and PEX5S, and we show that the c.722dupA mutation, located in the PEX5L-specific exon 9, results in loss of PEX5L only. Both PEX5 isoforms recognize PTS1-tagged proteins, but PEX5L is also a co-receptor for PTS2-tagged proteins. Previous patients with PEX5 mutations had ZSD, mainly due to deficient import of PTS1-tagged proteins. Similarly to mutations in PEX7, loss of PEX5L results in deficient import of PTS2-tagged proteins only, thus causing RCDP instead of ZSD. We demonstrate that PEX5L expression restores the import of PTS2-tagged proteins in patient fibroblasts. Due to the biochemical overlap between RCDP1 and RCDP5, sequencing of PEX7 and exon 9 in PEX5 should be performed in patients with a selective defect in the import of PTS2-tagged proteins., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

N,N-diethyl-m-toluamide (DEET), the active component of many insect repellents, is among the most frequently detected compounds in aqueous environments with concentrations reported in the ng L(-1) to μg L(-1) range. However, DEET is often detected in blanks and reported concentrations differ significantly depending on the analytical technique employed. In addition, relatively sparse data are available regarding the seasonal variability of DEET concentrations in water and there are apparent inconsistencies with expected use patterns. Therefore, the present study investigates potential interferences affecting the detection and quantification of DEET then the geographical and seasonal variations of DEET concentrations. To examine potential analytical interferences, DEET was analyzed in five geographically-diverse wastewater effluents using both gas chromatography and liquid chromatography coupled to mass spectrometric detectors. At times, the concentrations quantified by the employed analytical methods varied significantly. Five compounds with similar molecular weights and structures as DEET were investigated as potential mimics and some were shown to induce an overestimation of DEET. Further experimentation suggested that the solvents used in sample preparation and HPLC analysis are another possible source of interference. Besides potential interferences, the seven-month weekly monitoring of DEET in the primary effluent of a wastewater treatment plant demonstrated a clear seasonal trend with decreasing concentration from summer to winter. These data collectively demonstrate that there are many challenges in the quantification of DEET in complex environmental samples and that co-occurrence of similarly structured substances present in the water sample and/or the solvents used for the analysis could induce analytical bias., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In response to water scarcity, strategies relying on multiple processes to turn wastewater effluent into potable water are being increasingly considered by many cities. In such context, the occurrence of contaminants as well as their fate during treatment processes is a major concern. Three analytical approaches where used to characterize the efficacy of UV and UV/H2O2 processes on a secondary wastewater effluent. The first analytical approach assessed bulk organic parameters or surrogates before and after treatment, while the second analytical approach measured the removal of specific indicator compounds. Sixteen trace organic contaminants were selected due to their relative high concentration and detection frequency over eight monitoring campaigns. While their removal rate ranges from approximately 10 to >90%, some of these compounds can be used to gauge process efficacy (or failure). The third analytical approach assessed the fate of unknown contaminants through high-resolution time-of-flight (TOF) mass spectrometry with advanced data processing and demonstrated the occurrence of several thousand organic compounds in the water. A heat map clearly evidenced compounds as recalcitrant or transformed by the UV processes applied. In addition, those chemicals with similar fate were grouped together into clusters to identify new indicator compounds. In this manuscript, each approach is evaluated with advantages and disadvantages compared., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Because neurodegenerative dementias are progressive and ultimately fatal, a palliative approach focusing on comfort, quality of life, and family support can have benefits for patients, families, and the health system. Elements of a palliative approach include discussion of prognosis and goals of care, completion of advance directives, and a thoughtful approach to common complications of advanced dementia. Physicians caring for patients with dementia should formulate a plan for end-of-life care in partnership with patients, families, and caregivers, and be prepared to manage common symptoms at the end of life in dementia, including pain and delirium., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Cyanobacteria in surface water are well known for their ability to form toxic blooms responsible for animal mortality and human poisoning. Accompanying major progress in science and technology, the state of knowledge of cyanotoxins has dramatically increased over the last two decades. The bibliometric approach applied in this study shows the evolution of research and identifies major gaps to be filled by future work. Although the publication rate has gradually increased from one hundred to three hundred articles per year since the 1990s, half of the literature available focuses on microcystins and another quarter on saxitoxins. Other cyanotoxins such as beta-N-methylamino-l-alanine or cylindrospermopsin remain vastly disregarded. Moreover, most of the publications deal with toxicity and ecology while other research areas, such as environmental and public health, require additional investigation. The analysis of the literature highlights the main journals for the communication of knowledge on cyanotoxins but also reveals that 90% of the research is originated from only ten countries. These countries are also those with the highest H-index and average number of citation per article. Nonetheless, the ranking of these countries is significantly altered when the amount of publications is normalized based on the population, the number of universities, the national gross domestic product or the government revenue. However, the lower amount of publications from Eastern Europe, Africa and South America could also reflect the lack of monitoring campaigns in these regions. This lack could potentially lead to the underestimation of the prevalence of toxic cyanobacterial blooms and the diversity of toxins worldwide., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Cyanobacteria are ubiquitous microorganisms considered as important contributors to the formation of Earth's atmosphere and nitrogen fixation. However, they are also frequently associated with toxic blooms. Indeed, the wide range of hepatotoxins, neurotoxins and dermatotoxins synthesized by these bacteria is a growing environmental and public health concern. This paper provides a state of the art on the occurrence and management of harmful cyanobacterial blooms in surface and drinking water, including economic impacts and research needs. Cyanobacterial blooms usually occur according to a combination of environmental factors e.g., nutrient concentration, water temperature, light intensity, salinity, water movement, stagnation and residence time, as well as several other variables. These environmental variables, in turn, have promoted the evolution and biosynthesis of strain-specific, gene-controlled metabolites (cyanotoxins) that are often harmful to aquatic and terrestrial life, including humans. Cyanotoxins are primarily produced intracellularly during the exponential growth phase. Release of toxins into water can occur during cell death or senescence but can also be due to evolutionary-derived or environmentally-mediated circumstances such as allelopathy or relatively sudden nutrient limitation. Consequently, when cyanobacterial blooms occur in drinking water resources, treatment has to remove both cyanobacteria (avoiding cell lysis and subsequent toxin release) and aqueous cyanotoxins previously released. Cells are usually removed with limited lysis by physical processes such as clarification or membrane filtration. However, aqueous toxins are usually removed by both physical retention, through adsorption on activated carbon or reverse osmosis, and chemical oxidation, through ozonation or chlorination. While the efficient oxidation of the more common cyanotoxins (microcystin, cylindrospermopsin, anatoxin and saxitoxin) has been extensively reported, the chemical and toxicological characterization of their by-products requires further investigation. In addition, future research should also investigate the removal of poorly considered cyanotoxins (β-methylamino-alanine, lyngbyatoxin or aplysiatoxin) as well as the economic impact of blooms., (© 2013 Elsevier Ltd. All rights reserved.)

Background: The widespread utilization of organic compounds in modern society and their dispersion through wastewater have resulted in extensive contamination of source and drinking waters. The vast majority of these compounds are not regulated in wastewater outfalls or in drinking water while trace amounts of certain compounds can impact aquatic wildlife. Hence it is prudent to monitor these contaminants in water sources until sufficient toxicological data relevant to humans becomes available. A method was developed for the analysis of 36 trace organic contaminants (TOrCs) including pharmaceuticals, pesticides, steroid hormones (androgens, progestins, and glucocorticoids), personal care products and polyfluorinated compounds (PFCs) using a single solid phase extraction (SPE) technique with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The method was applied to a variety of water matrices to demonstrate method performance and reliability., Results: UHPLC-MS/MS in both positive and negative electrospray ionization (ESI) modes was employed to achieve optimum sensitivity while reducing sample analysis time (<20 min) compared with previously published methods. The detection limits for most compounds was lower than 1.0 picogram on the column while reporting limits in water ranged from 0.1 to 15 ng/L based on the extraction of a 1 L sample and concentration to 1 mL. Recoveries in ultrapure water for most compounds were between 90-110%, while recoveries in surface water and wastewater were in the range of 39-121% and 38-141% respectively. The analytical method was successfully applied to analyze samples across several different water matrices including wastewater, groundwater, surface water and drinking water at different stages of the treatment. Among several compounds detected in wastewater, sucralose and TCPP showed the highest concentrations., Conclusion: The proposed method is sensitive, rapid and robust; hence it can be used to analyze a large variety of trace organic compounds in different water matrixes.

In temperate countries, the occurrence of cyanobacterial blooms threatens drinking water resources. Consequently, cyanotoxins are increasingly considered in water treatment, and their reactions with chlorine used to disinfect drinking water are particularly investigated. This study presents new elements for further understanding of cylindrospermopsin chlorination, through reactants and by-products monitoring, UV spectrum examination, and cytotoxicity assessment on human intestinal Caco-2 cells. On the one hand, the evolution of mixture UV spectrum indicated that cylindrospermopsin was quickly transformed at least into one intermediate by-product. While mass spectrometry experiments confirmed that cylindrospermopsin was almost totally transformed within 5 min, chlorine was consumed up to 20 min after the beginning of the reaction with a rate of 5 mol per mol of toxin. Then, LC-MS analysis gave rise to the formation of a third cylindrospermopsin by-product in addition to 5-chloro-cylindrospermopsin and cylindrospermopsic acid previously identified. Thanks to the accurate mass measurement provided by the LTQ-Orbitrap mass spectrometer, this new and stable chlorination by-product was assigned the chemical formula C(13)H(18)N(4)O(7)S. On the other hand, both of the mitochondrial and lysosomal activities measured on Caco-2 cells revealed that cylindrospermopsin chlorination significantly decreases mixture cytotoxicity., (Copyright 2010 Elsevier B.V. All rights reserved.)

The occurrence of cyanobacterial blooms is drastically increasing in temperate countries and drinking water resources are threatened. As a result, cyanotoxins should be considered in water treatment to protect human health. This study presents a state of the art on cyanotoxins in water and their behaviour towards chlorination, a common drinking water disinfection process. Chlorination efficiency on cyanotoxins alteration depends on pH, chlorine dose and oxidant nature. Microcystins and cylindrospermopsin are efficiently transformed by chlorine, with respectively 6 and 2 by-products identified. In addition, chlorination of microcystins and cylindrospermopsin is associated with a loss of acute toxicity. Even though they have been less investigated, saxitoxins and nodularins are also altered by chlorine. For these toxins, no by-products have been identified, but the chlorinated mixture does not show acute toxicity. On the contrary, the fact that anatoxin-a has a very slow reaction kinetics suggests that this toxin resists chlorination., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Drinking water disinfection by chlorine is known to reduce concentration of microcystin, but compounds formed are rarely considered. In this work the chlorination of microcystin-LR has been studied by monitoring reactants consumption and reaction products using the linear trap quad-Orbitrap (LTQ-Orbitrap) technology. Microcystin-LR was totally transformed within 2 min, meanwhile chlorine was consumed until 30 min with a rate of 12 mol per mol of toxin. Four new by-products of microcystin-LR were identified as well as their isomers: monochloro-microcystin, monochloro-dihydroxy-microcystin, dichloro-dihydroxy-microcystin and trichloro-hydroxy-microcystin. In addition, four new isomers were also observed, corresponding to the dihydroxy-microcystin already known. Besides, another compound previously observed was identified as monochloro-hydroxy-microcystin.